Allogeneic Mesenchymal Stem Cells in Osteoarthritis

A Randomized, Double Blind, Multicentric, Placebo Controlled, Phase -II Study Assessing the Safety and Efficacy of Intraarticular Ex-vivo Cultured Adult Allogeneic Mesenchymal Stem Cells in Patients With Osteoarthritis of Knee

This trial is planed to study if allogeneic mesenchymal stem cells would be safe and beneficial in osteoarthritis of knee joint. This is a double blind study. Different doses of stem cells will be used in this study.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of Knee
• Intervention / Treatment: Biological: Ex- vivo cultured adult allogeneic MSCs; Biological: Plasmalyte-A

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • Department of Orthopedics, M. S. Ramaiah Memorial Hospital
    • Manipal, Karnataka, India, 576 104
      • Department of Orthopedics, Kasturba Medical College
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Seth G. S. Medical College and KEM Hospital
    • Pune, Maharashtra, India, 411001
      • Jehangir Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226 014
      • Department of Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females in the age 40 - 70 years (both inclusive)
2. Radiographic evidence of grade 2 to 3 osteoarthritis based on the Kellgren and Lawrence radiographic criteria.
3. History of primary idiopathic osteoarthritis of the knee characterized by pain which requires intake of analgesics.
4. Self-reported difficulty in at least one of the following activities attributed to knee pain: lifting and carrying groceries, walking 400 metres, getting in and out of a chair, or going up and down stairs.
5. Patients who have been on stable medication which may be NSAIDs / Opioid or opiate analgesics, for the past three months.
6. Female patients of childbearing age must be willing to use accepted methods of contraception during the course of the study
7. Ability to provide written informed consent.

Exclusion Criteria:

1. Prior or ongoing medical conditions (e.g., concomitant illness, psychiatric condition, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
2. History of surgery, or major trauma to the study joint
3. Arthroscopy on the study joint in the previous 12 months
4. Signs of active study joint inflammation including redness, warmth, and/or, if qualifying with osteoarthritis of the knee, a large, bulging effusion of the study knee joint with the loss of normal contour of the joint at the screening visit or at the baseline examination
5. Patients who had received intraarticular steroids or hyaluronan within the last three months.
6. Infections in or around the knee.
7. Patients awaiting a replacement knee or hip joint
8. Patients with other conditions that cause pain
9. Patients with deformity of the knee joint.
10. Significantly incapacitated or disabled and would be categorized as ACR Functional Class IV (largely or wholly incapacitated), or unable to walk without assistive devices
11. Patients with other known rheumatic or inflammatory disease such as rheumatoid arthritis
12. Other pathologic lesions on x-rays of knee
13. Positive hepatitis B surface antigen, hepatitis C antibody test, Anti human immunodeficiency virus (HIV) antibody test, or RPR
14. History of Bleeding disorders
15. Known hypersensitivity to Hyaluronan products or animal sera
16. For women of child-bearing potential: positive pregnancy test or lactating [Females who are planning pregnancy within next one year should be excluded]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Plasmalyte-A; Single intraarticular dose of 2ml Plasmalyte	Biological: Plasmalyte-A; Single intraarticular dose of 2ml Plasmalyte followed by 2ml Hyaluronan
EXPERIMENTAL: Ex- vivo cultured adult allogeneic MSCs; Single intraarticular dose of allogeneic MSCs suspended in 2-4ml Plasmalyte A followed by 2 ml of Hyaluronan	Biological: Ex- vivo cultured adult allogeneic MSCs; Single intraarticular dose of allogeneic MSCs suspended in 2ml Plasmalyte followed by 2ml of Hyaluronan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and percentage of patients with adverse events as a measure of safety and tolerability	Safety evaluation will include assessment of physical examination, periodic monitoring of vital signs (heart rate, respiratory rate, blood pressure and temperature), clinical laboratory investigations (including haematology, serum chemistry, LFT, urine-analysis) and 12-lead ECG recording.; Tolerability: Adverse events monitored using information volunteered by the patients and as observed by the PI will be summarized descriptively by total number of AE(s) and compared between the study arms.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the WOMAC OA (Western Ontario and McMaster Universities Osteoarthritis) Index -pain subscale score	2 years
Change from baseline in WOMAC OA stiffness index	2 years
Change from baseline in WOMAC OA composite index	2 years
Change from baseline in ICOAP (Intermittent and Constant Osteoarthritis Pain)	2 years
Change from baseline in radiographic (X-ray) findings of knee	2 years
Change from baseline in the WORMS score (Whole-Organ Magnetic Resonance Imaging Score) of knee using MRI	2 years
Change from baseline in arthritis pain scores on the visual analogue scale	2 years
Reduction in the intake of analgesic tablets from baseline	2 years

Collaborators and Investigators

• Sponsor: Stempeutics Research Pvt Ltd
• Investigators: Principal Investigator: Vikas Agarwal, MD., DM, Department of Immunology Sanjay Gandhi Post Graduate Institute of Medical Sciences; Principal Investigator: Vivek Pandey, MS, Department of Orthopedics, Kasturba Medical College; Principal Investigator: Naresh Shetty, MS, Department of Orthopedics, M. S. Ramaiah Memorial Hospital; Principal Investigator: Shrikant Wagh, MD, Jehangir Hospital; Principal Investigator: Bhibas Dasgupta, MS, Seth G. S. Medical College and KEM Hospital

Publications and helpful links

General Publications

• Gupta PK, Chullikana A, Rengasamy M, Shetty N, Pandey V, Agarwal V, Wagh SY, Vellotare PK, Damodaran D, Viswanathan P, Thej C, Balasubramanian S, Majumdar AS. Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel(R)): preclinical and clinical trial in osteoarthritis of the knee joint. Arthritis Res Ther. 2016 Dec 20;18(1):301. doi: 10.1186/s13075-016-1195-7.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: October 13, 2011
• First Submitted That Met QC Criteria: October 17, 2011
• First Posted (ESTIMATE): October 18, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 11, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Osteoarthritis; Stem cells; Knee; Mesenchymal Stem Cells
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: SRPL/OA/09-10/001